Olefin metathesis is a powerful method for the construction of C═C bonds in a large number of synthetic contexts, including target oriented synthesis, (see Metathesis in Natural Product Synthesis: Strategies, Substrates, and Catalysts; 1st ed.; Cossy, J., Arseniyadis, S., Meyer, C., Eds.; Wiley-VCH: Weinheim, Germany, 2010. Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem. Int. Ed. 2005, 44, 4490-4527) polymer chemistry, (see Handbook of Metathesis; Grubbs, R., Ed.; Wiley-VCH: Weinheim, Germany, 2003; Sutthasupa, S.; Shiotsuki, M.; Sanda, F. Polym. J. 2010, 42, 905-915) and renewable feedstock derivatization (see Nickel, A.; Pedersen, R. L. In Olefin Metathesis: Theory and Practice; Grela, K., Ed.; Wiley-VCH: Weinheim, Germany, 2014). Extensive efforts have been made to design tailored catalysts for each application (see Vougioukalakis, G. C.; Grubbs, R. H. Chem. Rev. 2010, 110, 1746-1787). The development of asymmetric olefin metathesis catalysts has enabled the synthesis of enantioenriched compounds containing olefin functional groups, which are useful functional handles for further transformations. Generations of Mo- and Ru-based catalysts have been applied to asymmetric ring opening cross metathesis (AROCM), asymmetric ring closing metathesis (ARCM), asymmetric ring rearrangements (ARR) and asymmetric cross metathesis (ACM) to the synthesis of useful synthetic building blocks and natural products (Scheme 1) (see Stenne, B.; Collins, S. K. In Olefin Metathesis: Theory and Practice; Grela, K., Ed.; Wiley-VCH: Weinheim, Germany, 2014; Hoveyda, A. H.; Malcolmson, S. J.; Meek, S. J.; Zhugralin, A. R. Angew. Chem. Int. Ed Engl. 2010, 49, 34-44. Hoveyda, A. H. J. Org. Chem. 2014, 79, 4763-4792).

Despite progress in catalyst design, however, significant challenges remain. Controlling olefin geometry in AROCM and ACM while maintaining high enantioselectivity is difficult. Furthermore, ARCM of unhindered trienes has so far been unsuccessful, resulting in extremely low enantioselectivities.
The first chiral Ru-based catalyst 1 as shown in Scheme 2, (see Seiders, T. J.; Ward, D. W.; Grubbs, R. H. Org. Lett. 2001, 3, 3225-3228) possessed a C2-symmetric NHC ligand with chiral centers on the backbone of the NHC and unsymmetrical N-aryl substituents. This chiral information was relayed to the metal center through a gearing effect (see Costabile, C.; Cavallo, L. J. Am. Chem. Soc. 2004, 126, 9592-9600). Complex 1 catalyzed desymmetrizing ARCM to afford dihydropyrans in high ee. It was found that substitution of chloride for iodide ligands resulted in higher ee but lower yield. The highest levels of enantioinduction were obtained on substrates with E-trisubstituted enantiotopic olefins; Z-trisubstituted or 1,1-disubstituted enantiotopic olefins reacted with much lower selectivity. Subsequent modifications of the N-aryl substituents resulted in a more selective catalyst 2 (see Funk, T. W.; Berlin, J. M.; Grubbs, R. H. J. Am. Chem. Soc. 2006, 128, 1840-1846) for ARCM and AROCM, although the latter transformation took place with poor E/Z selectivity (see Berlin, J. M.; Goldberg, S. D.; Grubbs, R. H. Angew. Chem. Int. Ed. 2006, 45, 7591-7595). C1-symmetric NHC ligands employing a geared arene substituent have also been developed by Collins (see Fournier, P.-A.; Collins, S. K. Organometallics 2007, 26, 2945-2949, Fournier, P.-A.; Savoie, J.; Stenne, B.; Bedard, M.; Grandbois, A.; Collins, S. K. Chem.-Eur. J. 2008, 14, 8690-8695. Grandbois, A.; Collins, S. K. Chem.-Eur. J. 2008, 14, 9323-9329. Savoie, J.; Stenne, B.; Collins, S. K. Adv. Synth. Catal. 2009, 351, 1826-1832) and Blechert (see Tiede, S.; Berger, A.; Schlesiger, D.; Rost, D.; Lühl, A.; Blechert, S. Angew. Chem. Int. Ed. 2010, 49, 3972-3975; Kannenberg, A.; Rost, D.; Eibauer, S.; Tiede, S.; Blechert, S. Angew. Chem. Int. Ed. 2011, 50, 3299-3302). For example, C1-symmetric catalyst 3 was capable of performing ARCM to generate tetrasubstituted olefins with good enantioselectivity (see Stenne, B.; Timperio, J.; Savoie, J.; Dudding, T.; Collins, S. K. Org. Lett. 2010, 12, 2032-2035).

Hoveyda has developed stereogenic-at-Ru complexes bearing a binaphthyl aryloxide NHC substituent (see Van Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.; Hoveyda, A. H. J. Am. Chem. Soc. 2002, 124, 4954-4955, Van Veldhuizen, J. J.; Gillingham, D. G.; Garber, S. B.; Kataoka, O.; Hoveyda, A. H. J. Am. Chem. Soc. 2003, 125, 12502-12508).
These complexes, which can be isolated as a single diastereomer, were used in E-selective AROCM and ARCM of trienes containing disubstituted enantiotopic olefins. Later a modified complex 4 containing NHC backbone chirality and a biphenyl aryloxide substituent was reported to have improved activity in E-selective AROCM of terminal olefins, (see Van Veldhuizen, J. J.; Campbell, J. E.; Giudici, R. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2005, 127, 6877-6882) and to catalyze Z-selective AROCM with vinyl ethers and vinyl sulfides (see Khan, R. K. M.; O'Brien, R. V.; Torker, S.; Li, B.; Hoveyda, A. H. J. Am. Chem. Soc. 2012, 134, 12774-12779). Subsequent studies demonstrated that a higher energy diastereomer (differing in configuration at Ru) is accessible. These diastereomers can interconvert either through olefin metathesis, or a non-metathesis based polytopal rearrangement, thermal or Brønsted acid catalyzed, (see Khan, R. K. M.; Zhugralin, A. R.; Torker, S.; O'Brien, R. V.; Lombardi, P. J.; Hoveyda, A. H. J. Am. Chem. Soc. 2012, 134, 12438-12441, Torker, S.; Khan, R. K. M.; Hoveyda, A. H. J. Am. Chem. Soc. 2014, 136, 3439-3455).
Substantial progress has been made in the development of cyclometalated Ru complexes such as (rac)-5, which catalyze the Z-selective cross metathesis of terminal olefins (see Endo, K.; Grubbs, R. H. J. Am. Chem. Soc. 2011, 133, 8525-8527, Keitz, B. K.; Endo, K.; Herbert, M. B.; Grubbs, R. H. J. Am. Chem. Soc. 2011, 133, 9686-9688, Herbert, M. B.; Lan, Y.; Keitz, B. K.; Liu, P.; Endo, K.; Day, M. W.; Houk, K. N.; Grubbs, R. H. J. Am. Chem. Soc. 2012, 134, 7861-7866, Keitz, B. K.; Endo, K.; Patel, P. R.; Herbert, M. B.; Grubbs, R. H. J. Am. Chem. Soc. 2012, 134, 693-699, Quigley, B. L.; Grubbs, R. H. Chem. Sci. 2013, 5, 501-506, Rosebrugh, L. E.; Herbert, M. B.; Marx, V. M.; Keitz, B. K.; Grubbs, R. H. J. Am. Chem. Soc. 2013, 135, 1276-1279).
Despite the advances achieved in the art, a continuing need exists for further improvements in the areas of Asymmetric Ring Opening Cross Metathesis (AROCM), Asymmetric Ring Closing Metathesis (ARCM), and Asymmetric Cross Metathesis (ACM). The present invention is directed to addressing one or more of those concerns.